The proposed research is designed to increase the understanding of regional differences in sensitivity and responsiveness of coronary, cerebral and peripheral arterial and venous smooth muscle. An attempt will be made to correlate regional variations in calcium binding characteristics within these vessels with differential reactivity to specific vasoconstrictors and vasodilators. The hypothesis to be tested is that certain stimulatory or inhibitory agents have a variation in the predominant component of calcium kinetics associated with its ionic basis of action in one vascular segment when compared to its action in a smaller segment within the same bed or between vessels of similar caliber is another bed. Initially variations in sensitivities, potencies and the importance of extracellular calcium in the total tension response to each agonist will be evaluated in main vessels and branches (capacitance and resistance). These vessels will then be characterized for total 45Ca binding, release and translocation. Subsequent studies will compare the action and interactions of stimulatory and inhibitory agents on lanthanum resistant calcium binding sites. A careful and extensive comparison of sensitivities, responsiveness, and susceptibility to calcium depletion, correlated with variations in calcium binding and translocation in a cross section of main vessels and branches should provide a solid base for making valid conclusions on activator sources of calcium in small resistance vessels and isolated arterioles. The manner in which different agents affect calcium stores and movements to alter vascular tone may remain the same from vessel to vessel, while the capacity or quantity of specific calcium stores may vary. Thus, this approach would not only increase the understanding of calcium binding characteristics regionally, but also increase the understanding of mechanisms of action and interaction at the cellular level, and possibly explain the greater sensitivity of specific vascular beds to certain vasoactive compounds.